Department of Human Metabolism, School of Medicine, University of Sheffield, Sheffield, UK.
J Invest Dermatol. 2010 Jan;130(1):230-40. doi: 10.1038/jid.2009.207.
Vitiligo is an acquired idiopathic hypomelanotic disorder characterized by circumscribed depigmented macules resulting from the loss of cutaneous melanocytes. Although the exact cause of vitiligo remains obscure, autoimmunity may play a role in the development of the disease. The present study was undertaken to investigate the applicability of phage display technology to identify B-cell autoantigens in vitiligo. A melanocyte cDNA phage display library was subjected to rounds of enrichment with vitiligo patient IgG. Subsequently, enriched IgG-binding peptides representing putative autoantigens were identified by sequencing their encoding cDNAs. Radioimmunoassays were used to confirm the immunoreactivity of vitiligo patient (n=61) and control (n=28) sera to several of the putative autoantigens. Non-segmental vitiligo patient sera (n=53) were positive for antibody (Ab) reactivity to gamma-enolase (8%); alpha-enolase (9%); heat-shock protein 90 (13%); osteopontin (4%); ubiquitin-conjugating enzyme (15%); translation-initiation factor 2 (6%); and GTP-binding protein, Rab38 (15%). Ab reactivity to at least one of the previously unknown autoantigens was detected in 51% of patients with non-segmental vitiligo. In contrast, Ab reactivity in a group of patients with segmental vitiligo (n=8) was not demonstrated. Overall, the study indicated that the targets of autoantibodies in vitiligo patients can be revealed by employing the methodology of phage display.
白癜风是一种获得性特发性色素减退症,其特征是皮肤黑素细胞丧失导致局限性脱色斑。虽然白癜风的确切病因仍不清楚,但自身免疫可能在疾病的发展中起作用。本研究旨在探讨噬菌体展示技术在鉴定白癜风 B 细胞自身抗原中的应用。用白癜风患者 IgG 对黑素细胞 cDNA 噬菌体展示文库进行多轮富集。随后,通过测序其编码 cDNA 来鉴定代表潜在自身抗原的富集 IgG 结合肽。放射免疫测定法用于确认若干潜在自身抗原的白癜风患者(n=61)和对照(n=28)血清的免疫反应性。非节段性白癜风患者血清(n=53)对γ-烯醇化酶(8%)、α-烯醇化酶(9%)、热休克蛋白 90(13%)、骨桥蛋白(4%)、泛素结合酶(15%)、翻译起始因子 2(6%)和 GTP 结合蛋白 Rab38(15%)具有抗体(Ab)反应性。在 51%的非节段性白癜风患者中检测到至少一种先前未知的自身抗原的 Ab 反应性。相比之下,在一组节段性白癜风患者(n=8)中未检测到 Ab 反应性。总的来说,该研究表明,通过采用噬菌体展示技术,可以揭示白癜风患者自身抗体的靶标。